Ulcerative colitis resident survival guide

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mugilan Poongkunran M.B.B.S [2]

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Overview

Ulcerative colitis (UC) is a chronic disease characterized by recurrent episodes of diffuse inflammation limited to the mucosal layer of the colon and presenting commonly as bloody diarrhea with rectal urgency and tenesmus. It commonly involves the rectum and may extend proximally in a symmetrical, circumferential, and uninterrupted pattern to involve parts of or even the entire large intestine.

Causes

Life Threatening Causes

Ulcerative colitis (UC) can be a life-threatening condition and must be treated as such irrespective of the underlying cause.

Common Triggers

Common factors recognized to exacerbate UC are:

• Campylobacter
• Clostridium difficile infection
• NSAIDS
• Salmonella
• Shigella

Management

Initial Approach

The algorithm is based on the American College of Gastroenterology guidelines for management of Ulcerative colitis (UC) in adults.

Characterize the symptoms: ❑ Diarrhea (onset, duration, pattern, frequency, type) ❑ Bowel urgency, tenesmus, and incontinence ❑ Abdominal pain ❑ Rectal bleeding ❑ Constipation ❑ Fever ❑ Fatigue ❑ Nausea ❑ Vomiting ❑ Abdominal distention ❑ Loss of appetite ❑ Loss of weight ❑ Mental status change Inquire about extraintestinal symptoms: ❑ Skin lesions ❑ Joint pains ❑ Cough, breathlessness ❑ Eyes (burning, itching, or redness) Obtain a detailed history: ❑ Recent travel ❑ Recent antibiotic, or NSAID, or isotretinoin use ❑ Abdominal or pelvic radiation ❑ Family history ❑ Systemic illness ❑ Personal history: Smoking

Assess volume status: ❑ General condition ❑ Thirst ❑ Pulse ❑ Blood pressure ❑ Eyes ❑ Mucosa Examine the patient: ❑ Skin (swelling, pain, erythema or ulceration) ❑ Abdomen (mass, distension or tenderness) ❑ Respiratory system (wheeze or crackles) ❑ Cardiovascular system ❑ Anorectal (bleeding) ❑ Eyes (swelling, pain, edema or vision loss) ❑ Musculoskeletal (axial, large and small joints)

Order tests: ❑ Complete blood count (CBC) ❑ Erythrocyte sedimentation rate (ESR) ❑ C-reactive protein (CRP) ❑ Serum electrolytes ❑ Total serum protein and albumin ❑ Stool analysis (occult blood, WBC's, calprotectin, culture, ova and parasites) ❑ Stool for Clostridium difficile toxin in case of recent hospitalization or antibiotic use ❑ Urinalysis ❑ BUN ❑ Creatinine ❑ Serum glucose ❑ Liver function tests ❑ Serologic testing for amoeba ❑ STD's: VDRL, PCR (HSV), gonococcal culture

Order confirmatory diagnostic tests: ❑ Colonoscopy and biopsy ❑ Proctosigmoidoscopy and biopsy ❑ Ileocolonoscopy ❑ Computed tomography (CT) ❑ Barium enema ❑ Magnetic resonance imaging

Confirm the diagnosis of UC: ❑ Findings on proctosigmoidoscopy or colonoscopy ❑ Symmetric, continuous, and circumferential lesions ❑ Rectum involvement (95%) ❑ Findings on histopathology ❑ Mucosal inflammation, noncaseating granuloma, villous atrophy, crypt abscess ❑ Backwash ileitis ❑ Negative stool examination for infectious causes

❑ Assess the severity

Mild ❑ < 4 loose stools per day (+/- blood) ❑ No dehydration ❑ Mild crampy pain ❑ No fever ❑ Normal hemoglobin ❑ Normal ESR

Moderate ❑ > 4 loose stools per day (+/- blood) ❑ Mild dehydration ❑ Abdominal pain that is not severe ❑ Low grade fever ❑ Mild anemia not requiring blood transfusions

Severe ❑ ≥6 loose bloody stools per day ❑ Moderate to severe dehydration ❑ Severe abdominal cramps ❑ High fever (temperature ≥37.5ºC) ❑ HR ≥90 beats/minute ❑ Hemoglobin <10.5 g/dL ❑ Elevated ESR (≥30 mm/hour) ❑ Rapid weight loss

Fulminant ❑ > 10 loose stools per day ❑ Continuous bleeding ❑ Severe dehydration ❑ Severe abdominal pain ❑ Abdominal distension ❑ High fever (temperature ≥37.5ºC) ❑ HR ≥90 beats/minute ❑ Hemoglobin <10.5 g/dL ❑ Elevated ESR (≥30 mm/hour) ❑ Rapid weight loss

Management of Mild to Moderate Ulcerative Colitis

Mild-moderate ulcerative colitis ❑ Outpatient therapy ❑ Oral rehydration therapy as per stool loss or frequency ❑ Symptomatic therapy: Anti-motility agents: Loperamide Anticholinergic agents: Propantheline, dicyclomine, or hyoscyamine

Distal colitis

Extensive colitis

Distal 5-8 cm of the rectum (Proctitis)

Greater than 8 cm of distal rectum (Proctosigmoiditis)

Topical (rectal) 5-aminosalicylic acid (5-ASA) ❑ Mesalamine suppositories: 500 mg BID or 1 g OD OR Consider topical (rectal) steroids ❑ Hydrocortisone suppository: 30 mg BID

Topical (rectal) 5-aminosalicylic acid (5-ASA) ❑ Mesalamine enemas: 1-4 g BID PLUS ❑ Mesalamine suppositories: 500 mg BID or 1 g OD OR Consider topical (rectal) steroids ❑ Hydrocortisone enema/foam: 100 mg BID PLUS ❑ Hydrocortisone suppository: 30 mg BID

Combination of oral and topical therapy ❑ Oral sulfasalazine: Titrated up to 4-6 g/day Or ❑ Oral nonsulfonamide 5-ASA: At least 2 g/day, titrating up to 4.8 g/day of the active 5-ASA moiety PLUS ❑ 5-ASA enemas (1-4 g) and 5-ASA suppositories (500 mg): BID Or ❑ Steroid foam (100 mg) and/or suppositories (30 mg): BID ❑ Symptoms so troubling, start with oral steroid therapy

Response to Rx in 4-6 wks

Response to Rx in 4-6 wks

Response to Rx in 2-4 wks

Yes

No

No

Yes

No

Yes

Maintenance therapy ❑ ONLY Rx patients with > 1 relapse a year ❑ Mesalamine suppositories: 500 mg BID or OD

Combination of oral 5-ASA and topical 5-ASA ❑ Oral sulfasalazine: 4-6 g/day in four divided doses Or ❑ Oral mesalamine: 2-4.8 g/day in three divided doses Or ❑ Oral balsalazide: 6.75 g/day in three divided doses Or ❑ Oral olsalazine: 1.5-3 g/day in two divided doses ❑Start at the lower dose and increase to the maximum tolerated dose OR Combination of topical 5-ASA and topical steroids ❑ Same dosage

Combination of oral 5-ASA and topical 5-ASA ❑ Start from a higher dose OR Combination of topical 5-ASA and topical steroids ❑ Same dosage

Maintenance therapy ❑ Rx all patients after the 1st episode ❑ Mesalamine enemas: 2-4 g/day at bedtime

Oral glucocorticoids ❑ Oral prednisolone: 40-60 mg one or in two divided doses

Maintenance therapy ❑ Oral sulfasalazine: 4-6 g/day in four divided doses PLUS ❑ Mesalamine suppositories: 1 g/day at bedtime Or ❑ Mesalamine enemas: 2-4 g/day at bedtime

On remission for 2 years without any relapses

Multiple relapses on maintenance therapy

Response to Rx in 2-4 wks

Multiple relapses on maintenance therapy

On remission for 2 years without any relapses

Response to Rx in 2-4 wks

Discontinue maintenance therapy

Rx with oral 5-ASA for remission and maintenance

Rx with oral 5-ASA for remission and maintenance

Discontinue maintenance therapy

No

Yes

Yes

No

Maintenance therapy ❑ Oral sulfasalazine: 2 g/day Or ❑ Eudragit-S-coated mesalamine: 3.2 g/day Or ❑ Extended release mesalamine capsules: 1.5 g/day in four divided doses Or ❑ Oral balsalazide: 3-6 g/day in three divided doses Or ❑ Oral olsalazine: 1 g/day in two divided doses Or ❑ Combination therapy: Oral mesalamine 1.6 g/day and enema 4g biweekly

Rx as extensive colitis ❑ Oral glucocorticoids Or ❑ IV infliximab

Intravenous steroids ❑ Inpatient therapy ❑ IV prednisolone: 30 mg/12 hrs Or ❑ IV methylprednisolone: 16-20 mg/8 hrs Or ❑ IV hydrocortisone: 100 mg/8 hrs

❑ Taper dose by 5-10 mg/wk over 8 wks until it is 20 mg/day ❑ Then taper dose by 2.5 mg/week and stop

Response to Rx in 7-10 days

No

Yes

Failure of maintenance therapy ❑ 6-mercaptopurine (6-MP): 1.5 mg/kg Or ❑ Azathioprine: 2-2.5 mg/kg Or ❑ IV infliximab: 5 mg/kg at 0, 2, and 6 wks

Steroid resistant UC therapy ❑ Azathioprine: 1.5-2.5 mg/kg/day Or ❑ 6-mercaptopurine (6-MP): 1.5 mg/kg/day

Switch to oral prednisone (40-60 mg) and start tapering its dose as mentioned above

Response to Rx

Relapse on tapering

Yes

No

Yes

No

Maintenance therapy ❑ 6-mercaptopurine (6-MP): 1.5 mg/kg Or ❑ Azathioprine:2-2.5 mg/kg Or ❑ IV infliximab: 5-10 mg/kg at 0, 2, and 6 wks

Steroid dependent UC therapy ❑ IV infliximab: 5-10 mg/kg at 0, 2, and 6 week and thereafter every 8 weeks Or ❑ SC adalimumab: 160 mg at week 0, 80 mg at week 2, and then 40 mg every 2 weeks

Maintenance therapy ❑ Oral sulfasalazine: 4-6 g/day in four divided doses PLUS ❑ Mesalamine suppositories: 1 g/day at bedtime Or ❑ Mesalamine enemas: 2-4 g/day at bedtime

Failure of treatment ❑ Surgical consultation for colectomy

Failure of maintenance therapy ❑ 6-mercaptopurine (6-MP): 1.5 mg/kg Or ❑ Azathioprine:2-2.5 mg/kg Or ❑ IV infliximab: 5-10 mg/kg at 0, 2, and 6 wks

Management of Severe and Fulminant Ulcerative Colitis

Severe colitis ❑ Outpatient/ Inpatient treatment as per symptom severity ❑ Oral rehydration therapy/ intravenous fluids ❑ Avoid complete colonoscopy ❑ Avoid anticholinergic, antidiarrheal agents, NSAIDs, and opioid drugs

Fulminant colitis ❑ Inpatient therapy ❑ NPO ❑ Intravenous fluids ❑ Avoid complete colonoscopy ❑ Total parental nutrition ❑ Blood transfusions to have hemoglobin ≥10 g/dL ❑ Monitor vitals every 4-6 hours ❑ Record the stool output ❑ Avoid anticholinergic, antidiarrheal agents, NSAIDs, and opioid drugs

Oral glucocorticoids ❑ Oral prednisolone: 40-60 mg one or in two divided doses PLUS High dose oral 5-aminosalicylic acid ❑ Oral sulfasalazine: 4-6 g/day Or ❑ Oral mesalamine:4.8 g/day Or ❑ Oral balsalazide: 6.75 g/day PLUS Topical therapy ❑ 5-ASA or steroid suppository PLUS ❑ 5-ASA, steroid enema, or foam

No toxic megacolon

Toxic megacolon (Colonic diameter ≥6 cm or cecum >9 cm and systemic toxicity)

Response to Rx in 2-4 weeks

Yes

No

❑ Taper the dose of steroids as mentioned above ❑ Monitor for any relapses and treat accordingly ❑ Start the patient on maintenance therapy as above

Inpatient management ❑ NPO ❑ Intravenous fluids: Normal saline or ringer lactate Intravenous steroids ❑ IV prednisolone: 30 mg/12 hrs Or ❑ IV methylprednisolone: 16-20 mg/8 hrs Or ❑ IV hydrocortisone: 100 mg/8 hrs Broad-spectrum antibiotics ❑ IV ciprofloxacin PLUS ❑ IV metronidazole: Venous thromboembolism prophylaxis

Inpatient management ❑Nasoenteric tube decompression Or ❑ Intermittent rolling maneuvers every 2 hrs Or ❑ Knee-elbow position Intravenous steroids ❑ IV prednisolone: 30 mg/12 hrs Or ❑ IV methylprednisolone: 16-20 mg/8 hrs Or ❑ IV hydrocortisone: 100 mg/8 hrs Broad-spectrum antibiotics ❑ IV ciprofloxacin PLUS ❑ IV metronidazole: Venous thromboembolism prophylaxis Immediate treatment for hypokalemia or hypomagnesemia

Response to Rx in 6-8 days

Response to Rx in 72 hrs

Yes

No

Yes

No

❑ Continue IV steroids till 10th day ❑ Switch to oral steroids and monitor the response ❑ Taper the dose of steroids as mentioned above ❑ Monitor for any relapses and treat accordingly ❑ Start the patient on maintenance therapy as above

❑ Continue IV steroids till 10th day ❑ Switch to oral steroids and monitor the response ❑ Taper the dose of steroids as mentioned above ❑ Monitor for any relapses and treat accordingly ❑ Start the patient on maintenance therapy as above

Surgical consultation for colectomy

Cyclosporine ❑ IV cyclosporine: 4 mg/kg per 24 hours as continuous infusion

Infliximab ❑ IV infliximab: 5-10 mg/kg

Response to Rx within 48-72 hrs

Response to Rx in 48-72 hrs

Yes

No

Yes

Bridging therapy ❑ Oral cyclosporine: 8 mg/kg/day as microemulsion ❑ Taper off the glucocorticoids over the first 4-6 weeks ❑ Taper off cyclosporine microemulsion over the next 6-8 weeks ❑ Start then 6-mercaptopurine (6-MP) or azathiopriner>

Surgical consultation for colectomy

❑ IV infliximab: 5-10 mg/kg at 2 and 6 wks and every 8 weeks thereafter

Do's

• Always first assess the volume status and correcting fluid and electrolyte disturbances take priority over the specific treatment in ulcerative colitis patients.
• Do perform a flexible sigmoidoscopy in hospitalized patients with severe colitis and the evaluation should be limited to the rectum and distal sigmoid colon.
• Do prescribe oral 5-ASA medications to patients who are unwilling or unable to tolerate topical medications.
• Do complete blood cell count and liver function tests at the initiation of 5-ASA therapy with subsequent monitoring every two weeks during the first three months, then monthly for the second three months, and every three months thereafter.
• Order serum blood urea nitrogen, creatinine and urinalysis testing at 6 weeks, 6 months, and 12 months after initiation of 5-ASA therapy and then annually.
• Order complete blood counts, initially every 1-2 weeks and at least every 3 months for patients on azathioprine, 6 mercaptopurine and other immunomodulator therapy to avoid the risk of acute or delayed bone marrow suppression.
• Always determine thiopurine methyltransferase (TPMT), the primary enzyme-metabolizing azathioprine/6-mercaptopurine, activity or genotype prior to initiating treatment with azathioprine or 6-mercaptopurine.
• Do monitor cyclosporine blood levels every one to two days after each dose change, and every two to three days when on stable doses.
• Do carefully monitor patients on cyclosporine for electrolyte abnormalities, nephrotoxicity, hypertension, neurotoxicity, and infections. Prophylaxis against Pneumocystis pneumonia (PCP) during therapy is required.
• Do reassess the extent of disease, compliance and consider coexisting conditions, if a patient has a recurrence of symptoms after initial improvement that does not mimic the initial presentation.
• Do recommend intravenous antibiotics (eg, ciprofloxacin and metronidazole) for all UC patients with high grade fever, leukocytosis and peritoneal signs or megacolon.
• Do a repeat stool analysis in patients with steroid-dependent or steroid-refractory ulcerative colitis in order to exclude a superimposed infection.
• Do recommend prophylaxis for venous thromboembolism for hospitalized ulcerative colitis patients.
• Do maintain IBD patients on glucocorticoids for more than 3 months, on calcium (1200 mg/day) and vitamin D (800 IU/day) through either diet and/or supplements.
• Absolute indications for surgery are exsanguinating hemorrhage, perforation, and documented or strongly suspected carcinoma.
• Do review the vaccination status of the patient at the time of diagnosis of UC and if live vaccines are required, they should be administered 4 to 12 weeks prior to the initiation of immunosuppression.
• Colonoscopic surveillance for cancer should begin after eight years in patients with pancolitis, and 15 years in patients with colitis involving the left colon and should be repeated every one to two years.

Dont's

• Don't treat patients with severe diarrheal dehydration using 5% dextrose with 1/4 normal saline, as using solutions with lower amounts of sodium (such as 38.5 mmol/L in 1/4 saline with 5% dextrose ) would lead to sudden and severe hyponatremia with a high risk of death.
• Oral rehydration therapy is contraindicated in the initial management of severe dehydration, in patients with frequent and persistent vomiting (more than four episodes per hour), and painful oral conditions such as moderate to severe thrush.
• Dont perform a full colonoscopy in hospitalized patients with severe colitis because of the potential to precipitate toxic megacolon.
• Dont use opiods, NSAID's, anticholinergic and antidiarrheal agents in patients with severe colitis because of the potential to precipitate toxic megacolon.
• Dont start maintenance therapy for patients with a first episode of mild ulcerative proctitis that has responded promptly to treatment.
• Dont use oral glucocorticoids for maintenance of remission.
• Dont taper steroids rapidly as it can cause early relapse and also may be associated with adrenal insufficiency.
• Dont continue oral 5-ASA medications if an ulcerative colitis flare coincides with a recent increase in dose or addition of the medication.
• Dont continue immunomodulator therapy in the occurrence of any hypersentivity reactions or any of their toxic side effects.
• Dont use infliximab in patients with active infection, untreated latent tuberculosis (TB), preexisting demyelinating disorder or optic neuritis, moderate to severe congestive heart failure, or current or recent malignancies.